1. Field of the Invention
The present invention relates to a process for the preparation of omega-arylalkanoic acids of the general formula. EQU R--Ar--R.sup.1 --COOH
wherein
R is hydrogen, hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 alkoxy, or aryl; PA1 R.sup.1 is C.sub.1 -C.sub.4 alkyl; and PA1 Ar is an aryl group which can be further substituted with at least one of hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 alkoxy, aryl, amino with the amino nitrogen bonded to hydrogen or C.sub.1 -C.sub.8 alkyl, or acetamido.
More particularly, this invention relates to an improved process for the preparation of omega-arylalkanoic acids via the Willgerodt-Kindler reaction and to methods of removing sulfur from the product produced by this improved process.
2. Background Information and Description of the Related Art
Omega-arylalkanoic acids are useful intermediates in the production of various chemicals and pharmaceuticals. For example, 4'-methoxyphenylacetic acid is an intermediate in the production of dextromethorphan, anti-cough medicine; homoveratic acid, obtained from 3,4-dimethoxyacetophenone (DMAP) is an important pharmaceutical intermediate; and 4-biphenylacetic acid, an analgesic, is produced from 4-acetylbiphenylacetophenone.
The omega-arylalkanoic acids can be synthesized from a thioamide which is produced via the Willgerodt-Kindler reaction. The thioamide can be synthesized by reaction of an aryl alkyl ketone or other starting material, sulfur and a primary or secondary amine. Following the preparation of the thioamide, it can be hydrolyzed to the corresponding omega-arylalkanoic acid.
The Willgerodt reaction is well known in the art as the reaction between an aryl alkyl ketone aqueous ammonium polysulfide to produce an aromatic amide and/or ammonium salt of the corresponding acid.
In addition to aryl alkyl ketones, the reaction has been shown to be applicable to the production of amides from other compounds such as dialkyl ketones, aliphatic mercaptans, secondary and tertiary alcohols, acetals and aromatic hydrocarbons. It is also known that a mixture of sulfur and ammonia is equivalent to ammonium polysulfide in obtaining the reaction.
In the Kindler modification of the Willgerodt reaction, an aryl alkyl ketone or other reactant can be reacted with sulfur and a primary or secondary amine such as morpholine and the product is the thioamide.
C. G. Joshi, in J. Sci. Ind. Res., 21B, 1962, 284-5, discloses a method for the preparation of arylacetic acids from aryl-alkyl ketones by a modification of the Willgerodt-Kindler reaction. This process involves the use of morpholine and sulfur in reflux with the ketone, followed by basification, cooling, filtration and acidification. However, this article does not disclose the use of a catalyst or the sulfur removal techniques disclosed in this application.
U.S. Pat. No. 2,489,348 issued Nov. 29, 1949 to Wenner discloses the production of arylacetic acids and amides. Some examples disclose the purification of the crude acids by basification, filtering and acidification to yield the free acids. However, the production method disclosed does not employ sulfur nor function in the manner of the Willgerodt-Kindler reaction.
F. Ansinger et al., in Monatshefte fur Chemie, 103, 1972, 1661-1668, disclose to the preparation of various materials comprising sulfur, nitrogen and aryl components, wherein acetophenone is treated with sulfur and amines. In particular, hexathiocanethiones were obtained by treating RC.sub.6 H.sub.4 COMe with R'NH.sub.2 and S in the presence of HOAc.